Balogh Edina, Tripier Raphaël, Ruloff Robert, Tóth Eva
Laboratoire de Chimie Inorganique et Bioinorganique, Ecole Polytechnique Fédérale de Lausanne, ISIC, BCH, CH-1015 Lausanne, Switzerland.
Dalton Trans. 2005 Mar 21(6):1058-65. doi: 10.1039/b418991d. Epub 2005 Feb 10.
The tetraazamacrocyclic ligand TRITA(4-) is intermediate in size between the widely studied and medically used 12-membered DOTA(4-) and the 14-membered TETA(4-). The kinetic inertness of GdTRITA(-) was characterized by the rates of exchange reactions with Zn(2+) and Eu(3+). In the Zn(2+) exchange, a second order [H(+)] dependence was found for the pseudo-first-order rate constant (k(0)=(4.2 +/- 0.5) x 10(-7) s(-1); k'=(3.5 +/- 0.3) x 10(-1) M(-1)s(-1), k" =(1.4 +/- 0.4) x 10(3) M(-2)s(-1)). In the Eu(3+) exchange, at pH <5 the rate decreases with increasing concentration of the exchanging ion, which can be accounted for by the transitional formation of dinuclear GdTRITAEu(2+) species. At physiological pH, the kinetic inertness of GdTRITA(-) is considerably lower than that of GdDOTA(-)(t(1/2)= 444 h (25 degrees C) vs. 3.8 x 10(5) h (37 degrees C), respectively). However, GdTRITA(-) is still kinetically more inert than GdDTPA(2-), the most commonly used MRI contrast agent (t(1/2)= 127 h). The formation reactions of LnTRITA(-) complexes (Ln = Ce, Gd and Yb) proceed via the rapid formation of a diprotonated intermediate and its subsequent deprotonation and rearrangement in a slow, OH(-) catalyzed process. The stability of the LnH(2)TRITA* intermediates (log K(LnH2L*)= 3.1-3.9) is lower than that of the DOTA-analogues. The rate constants of the OH(-) catalyzed step increase with decreasing lanthanide ion size, and are about twice as high as for DOTA-complexes.
四氮大环配体TRITA(4-)的大小介于广泛研究且用于医学的12元DOTA(4-)和14元TETA(4-)之间。GdTRITA(-)的动力学惰性通过与Zn(2+)和Eu(3+)的交换反应速率来表征。在Zn(2+)交换中，发现伪一级速率常数对[H(+)]呈二级依赖性(k(0)=(4.2±0.5)×10(-7) s(-1); k'=(3.5±0.3)×10(-1) M(-1)s(-1), k" =(1.4±0.4)×10(3) M(-2)s(-1))。在Eu(3+)交换中，在pH<5时，速率随交换离子浓度的增加而降低，这可以通过双核GdTRITAEu(2+)物种的过渡形成来解释。在生理pH下，GdTRITA(-)的动力学惰性明显低于GdDOTA(-)(半衰期分别为444小时(25℃)和3.8×10(5)小时(37℃))。然而，GdTRITA(-)在动力学上仍然比最常用的MRI造影剂GdDTPA(2-)更惰性(半衰期=127小时)。LnTRITA(-)配合物(Ln = Ce、Gd和Yb)的形成反应通过快速形成双质子化中间体及其随后在缓慢的OH(-)催化过程中的去质子化和重排进行。LnH(2)TRITA中间体的稳定性(log K(LnH2L) = 3.1 - 3.9)低于DOTA类似物。OH(-)催化步骤的速率常数随着镧系离子尺寸的减小而增加，并且大约是DOTA配合物的两倍。
